Dahniel Sastow, Hannah Levavi, Nicole Wagner, Keith Pratz, Douglas Tremblay
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引用次数: 0
Abstract
Older/unfit adults with AML have worse outcomes and fewer treatment options than their younger/fit counterparts. In vitro studies have found a synergistic effect of hypomethylating agents (HMA) with venetoclax (VEN) on AML cells and since the phase 3 VIALE-A trial demonstrated a survival benefit, HMA + VEN has become the standard of care in the frontline setting for older/unfit adults with AML. Unfortunately, the standard 28-day cycle of VEN is associated with a high degree of myelosuppression leading to treatment delays and dose modifications. Many small retrospective studies have successfully shown comparable outcomes to VIALE-A with reduced dose/duration of VEN. Furthermore, low dose metronomic dosing of HMA + VEN has shown clinical benefit while minimizing myelotoxicity. Future trials are vital to understand the appropriate dose of VEN in combination with HMA, to evaluate HMA + VEN compared to intensive therapy for younger/fit patients, and to explore its utility in the relapsed/refractory setting.
与年轻/身体健康的患者相比,老年/身体不健康的成人急性髓细胞白血病患者的治疗效果更差,治疗方案更少。体外研究发现,低甲基化药物(HMA)与 Venetoclax(VEN)对急性髓细胞白血病细胞有协同作用,自从 VIALE-A 3 期试验显示生存获益后,HMA + VEN 已成为急性髓细胞白血病老年/非适应症成人患者的一线治疗标准。遗憾的是,标准的 28 天 VEN 周期与高度骨髓抑制有关,导致治疗延迟和剂量调整。许多小型回顾性研究成功表明,在减少 VEN 剂量/疗程的情况下,疗效与 VIALE-A 相当。此外,HMA + VEN 的低剂量节律给药已显示出临床疗效,同时将骨髓毒性降至最低。未来的试验对于了解 VEN 与 HMA 联用的适当剂量、评估 HMA + VEN 与针对年轻/适合患者的强化治疗的比较以及探索其在复发/难治性病例中的应用至关重要。
期刊介绍:
Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.